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Drugs repurposed to potentiate immunotherapy for cancer treatment

Introduction Cancer is a leading cause of death worldwide. Given the unmet need for more effective anticancer therapy, intense efforts have been invested in searching for better anticancer drugs in a more efficient manner. Pharmaceutical companies and academic investigators alike have become increasingly interested in finding new uses of the existing drugs, a process referred to as drug repurposing or repositioning, to treat cancer. The existing…

Identification of chemosensitizers by drug repurposing to enhance the efficacy of cancer therapy

Acknowledgments A Ph.D. stipend of the Chinese Scholarship Council to G.Y. is gratefully acknowledged. Introduction The development of drug resistance, which eventually leads to therapy failure and tumor relapse, emerges as a major challenge in cancer treatment. Clinic drug resistance is featured by the resistance toward a broad spectrum of drugs, which are structurally and functionally unrelated, i.e., multidrug resistance (MDR). Both intrinsic and acquired drug resistance…

Animal models and in vivo investigations for drug repurposing in lung cancer

Introduction Lung cancer is one of the most common and serious types of cancer, which causes the highest cancer mortality among men and women worldwide. The two major types of lung cancers are small cell lung cancer (SCLC) and non-small cell lung cancer (NSCLC), based on histological differentiation. NSCLCs are further divided into squamous cell carcinomas (SCCs), pulmonary adenocarcinomas (ADC), and large cell carcinomas. Lung ADC…

Stories of drug repurposing for pancreatic cancer treatment—Past, present, and future

Acknowledgments We want to apologize to all authors whose work could not be cited due to space restrictions/limitations in this chapter. Introduction Cancer in general is one of the leading causes of mortality worldwide [ ]. Pancreatic ductal adenocarcinoma (PDAC), as the most frequent malignant tumor of the pancreas, has not a high incidence on a global level. However, it is projected to become the second…

Successful stories of drug repurposing for cancer therapy in hepatocellular carcinoma

Hepatocellular carcinoma Hepatocellular carcinoma (HCC) is a major health problem with devastating consequences associated with treatment failure. It has an estimated global incidence of more than 850,000 new cases annually [ ]. HCC is currently the second leading cause of cancer-related death worldwide and accounts for 90% of cases with primary liver cancer [ ]. Several risk factors contribute to HCC development such as liver cirrhosis,…

A personalized medicine approach to drug repurposing for the treatment of breast cancer molecular subtypes

Introduction Breast cancer is a major public health concern and a relevant mortality issue in young women worldwide [ ]. Mammary tumors are extremely heterogeneous at the histological, molecular, and systemic levels. To handle such variability, oncology researchers and clinicians have developed a number of prognostic and therapeutic approaches ranging from classifications based on clinical parameters or histopathologic markers (such as estrogen, progesterone, and epidermic human…

The success story of drug repurposing in breast cancer

Introduction Breast cancer is the most prevalent cancer in women worldwide, and despite tremendous research efforts, it remains the second leading cause of cancer-related mortalities among women ( ). According to the 2018 GLOBOCAN report, over 2 million new breast cancer incidences and nearly 600,000 deaths were reported globally [ ]. Breast cancer is vastly heterogeneous owing to differences in the underlying molecular architecture among…

Increasing opportunities of drug repurposing for treating breast cancer by the integration of molecular, histological, and systemic approaches

List of abbreviations 2-DG 2-Deoxyglucose 2-FDG 2-Fludeoxyglucose 3D Three direct-acting antivirals ABC7 Adjuvant for breast cancer treatment using seven repurposed drugs ABCG2 ATP-binding cassette superfamily G member 2 ADH Alcohol dehydrogenase ADRB Adrenoreceptor beta ALDH Aldehyde dehydrogenase AMP Adenosine monophosphate AMPK AMP-activated protein kinase ART Artemisinin ATP Adenosine triphosphate BCRP Breast cancer–resistance protein BCSCs Breast cancer stem cells BLBC Basal-like breast cancer BRCA-1 Breast cancer-1 CDDP…

Unveiling potential anticancer drugs through in silico drug repurposing approaches

List of abbreviations ABPP Activity-based protein profiling ADR Adverse drug reactions AI Artificial intelligence AML Acute myeloid leukemia ANN Artificial neural networks ATC Anatomical therapeutic classification AUC Area under curve AUROC Area under the receiver operating characteristic curve BBB Brain–blood barrier BSCE Basespace Correlation Engine CancerDR Cancer drug resistance CCLE Cancer Cell Line Encyclopedia CCLP Cancer cell line profiler CD Cancer drug CDK2 Cyclin-dependent kinase 2…

Machine learning strategies for identifying repurposed drugs for cancer therapy

Introduction The 2018 Nobel Prize in Physiology or Medicine was awarded to two researchers for their discovery of immune checkpoint proteins [ ]. Although the discovery initiated the development of the revolutionary targeted immunotherapies, critical challenges remain to be addressed, making them far from perfection [ ]. Limitations have been observed earlier in chemotherapies, where cytotoxic molecular compounds are administered to directly kill tumor cells and…

A ligand-centric approach to identify potential drugs for repurposing: case study with aurora kinase inhibitors

Acknowledgments The authors are thankful to OpenEye Scientific Software, Santa Fe, NM, USA, for providing access to free academic evaluation license. SC acknowledges the financial support by Department of Science and Technology, Government of India toward her research through DST-INSPIRE fellowship. PC is thankful to All India Council of Technical Education, Government of India for her GPAT scholarship. This research is supported by Mathematical Biology program…

Drug repurposing for cancer therapy—an introduction

Acknowledgments The authors wish to thank Andrea Leurs, KU Leuven, for assistance with the preparation of the data on drug repurposing clinical trials. Introduction It incumbent upon us to seek new therapeutic options for cancer patients wherever they may be found—including seeking to extend the use of existing medications to the treatment of new diseases. This strategy, variously termed drug repurposing or drug repositioning, is in…

Hemostatic Aspects of Sickle Cell Disease

Historical Perspective The seminal work of Pauling and colleagues on the properties of hemoglobin S provided the basis for a hypothesis that heralded the concept of “molecular medicine.” Indeed, sickle cell anemia a a SCD includes various genotypes, whereas Hb SS is referred to as SCA. Hb S-β 0 thalassemia has similar clinical features to Hb SS and may also be identified to as SCA. (SCA)…

Hemorrhage Control and Thrombosis Following Severe Injury

Introduction Injury is common. Small hospitals have emergency rooms, which deal with a spectrum of injuries, but intensive care of the most severely injured is highly centralized, taking place chiefly in regional trauma centers. It has been estimated that in the United States, 36 million people (one in every seven members of the population) are significantly injured each year. Three-quarters of the injured seek medical care,…

Paradoxical Embolic Stroke : Diagnosis and Management

Paradoxical embolization describes the passage of material, typically thrombus, from venous circulation into the systemic arterial circulation via a shunt. Presence of a right-to-left shunt is often the result of an atrial cardiac defect. In 1877, Dr. Julius Cohnheim, a Prussian pathologist, first proposed this mechanism after identifying a large atrial defect during the autopsy of a 35-year-old woman who suffered a fatal ischemic stroke. Three…

Hematologic Interventions for Acute Central Nervous System Disease

Introduction Acute central nervous system (CNS) diseases are notable for two critical features. The first, and perhaps most obvious, is that these are diseases that are life threatening and likely to cause major permanent neurologic disability. In short, the consequences of these diseases can be devastating to patients and their families. The second critical feature of acute CNS disease is the remarkable time sensitivity of most…

Outpatient Oral Anticoagulant Therapy

The coumarin-type oral anticoagulants have been in use for more than 70 years and are well-established weapons in the armamentarium against thrombotic disease. Their discovery evolved from investigations into a hemorrhagic disease of cattle occurring early in the 20th century attributed to the consumption of spoiled sweet clover. Karl P. Link, a biochemist at the University of Wisconsin, eventually isolated the responsible agent in spoiled sweet…

Understanding and Managing the Coagulopathy of Liver Disease

Introduction The liver plays a pivotal role in thrombosis and hemostasis because it synthesizes many hemostatic proteins. All procoagulant plasma proteins; the anticoagulant plasma proteins except for tissue factor pathway inhibitor; the fibrinolytic plasma proteins plasminogen, α 2 -antiplasmin, thrombin-activatable fibrinolysis inhibitor, and factor XIII; the von Willebrand factor (VWF)–cleaving protease ADAMTS13 ( a d isintegrin-like a nd m etalloprotease with t hrombo s pondin type…

Anticoagulation in the Perioperative Period

Millions of people in the United States are on antithrombotic therapy—either antiplatelet therapy or anticoagulants—for treatment and prevention of venous and arterial thromboembolism. During a given year, as many as 10% of these patients will need an invasive procedure. How to manage antithrombotic therapy during a procedure depends on multiple factors—the indication for therapy, the nature of the intervention, and the patient's risk for either bleeding…

Surgery and Hemostasis

By observing and studying the effects of surgery and trauma on hemostasis—including physiologic as well as hypocoagulable and hypercoagulable situations—our understanding of the interrelationship between hemostasis and surgery has been advanced. The following six topics will be addressed in this chapter using six subchapters: 1. Surgery for patients with congenital hemostatic defects 2. The general effects of surgery on hemostasis using cardiopulmonary bypass (CPB) and orthotopic…